Liposomal levamisole preparation and investigation of pharmacokinetic properties

LIPOSOMAL LEVAMISOLE PREPARATION AND INVESTIGATION OF PHARMACOKINETIC PROPERTIES When the livestock sector of our country is considered, sheep breeding constitutes an important part. Due to the diseases caused by parasites, it causes serious financial losses in products such as meat, milk, leaf and leather obtained from this sector and provided with economic income. Levamisole is a drug used for its antiparasitic and immune system enhancing effects in animals and humans. Liposomes are one of the drug formulations that have been studied a lot in recent years, especially with the increasing importance of nanotechnology in the treatment of diseases. There is no liposomal drug formulation for field use in veterinary medicine. In this research, a study was conducted to fill the gap in the field. In this research; liposomal levamisole preparation and investigation of its pharmacokinetic properties are intended. In the study, 7.5 mg/kg of levamisole in free and liposomal formulations was administered orally, subcutaneously and intramuscularly to sheep. The animals were divided into 2 groups to compare administration of free and liposomal levamisole. A total of 12 animals, 6 in each group, were included in the study. Taking into account the wash-out time of drug residues, 3 routes of administration were tried on 12 animals. Thin-lipit film hydration method was preferred for the preparation of liposomal formulation of levamisole. As a result of the quality control studies of liposomes; it was found that the encapsulation rate of levamisole was 31.41-32.34%, zeta potentials ranged from -16.2 to -1.6 mV, polydispersity indices were 0.231-0.998, pH values ranged from 6.75-7.04 layers. Pictures of the liposomes were taken under a scanning electron microscope. After administration of free and liposomal levamisole drug; at 2.5, 5, 10, 15, 30, 60, 90, 120, 240, 480 minutes; blood samples were taken at 12, 16, 24, 32, 48 hours and 3, 4, 5, 6, 8 days. For plasma drug measurements, quantification in HPLC was performed. The changes in the pharmacokinetic parameters of free and liposomal levamisole were assessed separately by route of administration. Pharmacokinetic parameters were statistically evaluated according to the application pathways. When administered orally, free and liposomal levamisole were compared in terms of pharmacokinetic parameters; Clast, EAA0-t, EAA0-∞, tmax, Cmax and ClT values were better with liposomal levamisole. When comparing free and liposomal levamisole administered subcutaneously in terms of pharmacokinetic parameters; Clast, EAA0-t, EAA0-∞, Cmax and ClT values were better with liposomal levamisole. Pharmacokinetic parameters were compared for intramuscular administration of free and liposomal levamisole; Clast, EAA0-t, EAA0-∞, Cmax and ClT values were better with liposomal levamisole. When comparing the pharmacokinetic parameters of liposomally, orally, subcutaneously and intramuscularly administered levamisole according to the routes of administration, it was found that tmax was higher for oral administration than for subcutaneous and intramuscular administration. If the Cmax values are compared according to the application routes; Although there is no significant difference between intramuscular and subcutaneous use; Both routes of administration were found to give better results than the oral route. When comparing oral, subcutaneous and intramuscular administrations of liposomal levamisole; It was found that the Clast, EAA0-t, EAA0-∞, Cmax and ClT values were better with intramuscular administration compared to the other two administrations. It was concluded that the most appropriate route is intramuscular and subcutaneous when the levamisole liposomal formulation is to be used in animals. However, it was concluded that it would be better to continue studies on liposomal drugs so that the results reflect the general animal population. Keywords: Pharmacokinetic, levamisole, liposome, HPLC.